IL31RA

Interleukin-31 receptor subunit alpha (IL31RA), also termed IL-31RA or IL-31Rα, is a transmembrane protein belonging to the type I cytokine receptor family. It dimerizes with oncostatin M receptor β (OSMRβ) to form the functional IL-31 receptor complex, which activates downstream signaling pathways including JAK/STAT, MAPK, and PI3K/AKT. IL-31 signaling is primarily implicated in mediating pruritus (itch) and inflammatory responses, particularly in epithelial and immune cells. This axis plays a critical role in skin barrier dysfunction and neuroimmune crosstalk, with aberrant IL31RA activity linked to pathological pruritus in allergic and autoimmune conditions.
Dysregulation of IL31RA is strongly associated with atopic dermatitis, allergic contact dermatitis, and prurigo nodularis. Therapeutic strategies targeting the IL-31/IL31RA axis have advanced significantly, with anti-IL-31 monoclonal antibodies like nemolizumab demonstrating efficacy in Phase III trials for moderate-to-severe atopic dermatitis and prurigo nodularis. These biologics alleviate itching by blocking IL-31 binding to its receptor, subsequently suppressing Th2-mediated inflammation and neuronal sensitization. Small-molecule inhibitors targeting downstream JAK kinases are also under investigation, offering potential oral alternatives for chronic pruritic diseases.